← Back to Search
Real Time Ultrasound Molecular Imaging Of Prostate Cancer With PSMA-targeted Nanobubbles
R. Perera, A. D. de Leon, Xinning Wang, Y. Wang, G. Ramamurthy, P. Peiris, Eric C Abenojar, J. Basilion, A. Exner
Published 2019 · Medicine, Biology
Download PDFAnalyze on Scholarcy
Contrast-enhanced ultrasound with microbubbles has shown promise in detection of prostate cancer (PCa), but sensitivity and specificity of detection remain challenging. Targeted nanoscale contrast agents with improved capability to accumulate in tumors may result in prolonged signal enhancement and improved detection of PCa with ultrasound. Here we report on a new nanobubble contrast agent that specifically targets prostate specific membrane antigen (PSMA) overexpressed in most prostate tumors. The PSMA-targeted bubbles (PSMA-NB) were utilized to simultaneously image dual flank PCa tumors (PSMA-positive PC3pip and PSMA-negative PC3flu) to examine whether the biomarker can be successfully detected and imaged using this probe in a mouse model. Results demonstrate that active targeting of NBs to PSMA rapidly and selectively enhances tumor accumulation and is critical for tumor retention of the contrast agent. Importantly, these processes could be visualized and quantified, in real time, with standard clinical ultrasound. Such demonstration of the immense yet underutilized potential of ultrasound in the area of molecular imaging can open the door to future opportunities for improving sensitivity and specificity of cancer detection using parametric NB-enhanced ultrasound imaging.
This paper references
CHAPTER THREE Ultrasound Contrast Agents and Delivery Systems in Cancer Detection and Therapy
A. D. de Leon (2018)
Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer.
M. M. Siddiqui (2015)
Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature.
S. S. Chang (1999)
Ultrasound Molecular Imaging With BR55 in Patients With Breast and Ovarian Lesions: First-in-Human Results.
J. Willmann (2017)
Annual Report to the Nation on the Status of Cancer, part I: National cancer statistics
K. Cronin (2018)
Location of Prostate Cancers Determined by Multiparametric and MRI-Guided Biopsy in Patients With Elevated Prostate-Specific Antigen Level and at Least One Negative Transrectal Ultrasound-Guided Biopsy.
M. Schouten (2015)
Then tissues were incubated in 1:150 diluted PSMA primary antibody
Magnetic resonance imaging-targeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound-guided biopsy: a systematic review and meta-analysis.
I. Schoots (2015)
Nanobubble Extravasation in Prostate Tumors Imaged with Ultrasound: Role of Active versus Passive Targeting
R. Perera (2018)
Role of transrectal ultrasonography (TRUS) in focal therapy of prostate cancer: report from a Consensus Panel
M. Smeenge (2012)
Toward attogram mass measurements in solution with suspended nanochannel resonators.
Jungchul Lee (2010)
EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013.
A. Heidenreich (2014)
Development of polymeric microbubbles targeted to prostate-specific membrane antigen as prototype of novel ultrasound contrast agents.
V. Sanna (2011)
Ultrasound Molecular Imaging of VEGFR2 in a Rat Prostate Tumor Model Using BR55
I. Tardy (2010)
Improving performance of nanoscale ultrasound contrast agents using N,N-diethylacrylamide stabilization.
R. Perera (2017)
Prostate-specific membrane antigen expression as a predictor of prostate cancer progression.
S. Perner (2007)
MRI-guided prostate biopsy detects clinically significant cancer: analysis of a cohort of 100 patients after previous negative TRUS biopsy
M. Roethke (2011)
Theranostic Agents for Photodynamic Therapy of Prostate Cancer by Targeting Prostate-Specific Membrane Antigen
X. Wang (2016)
Nanobubble Ultrasound Contrast Agents for Enhanced Delivery of Thermal Sensitizer to Tumors Undergoing Radiofrequency Ablation
Reshani H. Perera (2013)
Acoustic characterization and pharmacokinetic analyses of new nanobubble ultrasound contrast agents.
Hanping Wu (2013)
Detection of prostate cancer cells circulating in peripheral blood by reverse transcription-PCR for hKLK2.
M. Kawakami (1997)
Prostate cancer detection with magnetic resonance‐ultrasound fusion biopsy: The role of systematic and targeted biopsies
Christopher P. Filson (2016)
Development of prostate specific membrane antigen targeted ultrasound microbubbles using bioorthogonal chemistry
A. Zlitni (2017)
Annual Report to the Nation on the Status of Cancer, part II: Recent changes in prostate cancer trends and disease characteristics
Serban Negoita (2018)
Prostate‐specific membrane antigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivity and specificity in prostate adenocarcinoma: an immunohistochemical study using mutiple tumour tissue microarray technique
P. Mhawech-Fauceglia (2007)
Ultrasound imaging beyond the vasculature with new generation contrast agents.
R. Perera (2015)
The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo.
H. Maeda (2013)
Weighing nanoparticles in solution at the attogram scale
S. Olcum (2014)
Ultrasound molecular imaging of ovarian cancer with CA-125 targeted nanobubble contrast agents.
Y. Gao (2017)
Ultrasonic Nanobubbles Carrying Anti-PSMA Nanobody: Construction and Application in Prostate Cancer-Targeted Imaging
X. Fan (2015)
The prostate-specific membrane antigen: lessons and current clinical implications from 20 years of research.
B. Ristau (2014)
Effect of edge activators on the formation and transfection efficiency of ultradeformable liposomes.
Eun Hye Lee (2005)
Unpaired Student's t-test (two-tailed) was used to compare two groups. Data are presented as a mean ± STD (standard deviation). The experiments were repeated at least three times for each experiment
BR55: A Lipopeptide-Based VEGFR2-Targeted Ultrasound Contrast Agent for Molecular Imaging of Angiogenesis
S. Pochon (2010)
Comparison of PET/CT and PET/MRI hybrid systems using a 68Ga-labelled PSMA ligand for the diagnosis of recurrent prostate cancer: initial experience
A. Afshar-Oromieh (2013)
Universal Equations for the Coalescence Probability and Long-Term Size Stability of Phospholipid-Coated Monodisperse Microbubbles Formed by Flow Focusing.
T. Segers (2017)
Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment.
S. Hobbs (1998)
Effect of ligand density, receptor density, and nanoparticle size on cell targeting.
Drew R. Elias (2013)
"Targeting" nanoparticles: the constraints of physical laws and physical barriers.
A. Florence (2012)
Ultrasound molecular imaging: Moving toward clinical translation.
Lotfi Abou-Elkacem (2015)
Preparation and Evaluation of Radiolabeled Antibody Recruiting Small Molecules That Target Prostate-Specific Membrane Antigen for Combined Radiotherapy and Immunotherapy.
Afaf R. Genady (2016)
24 hrs at 4 o C. After washed with PBS, one-hour incubation of Alexa 568 tagged secondary antibody
Evaluation of Prostate-Specific Membrane Antigen as an Imaging Reporter
M. Castanares (2014)
Weighing of biomolecules, single cells and single nanoparticles in fluid
T. Burg (2007)
Nanobody-coupled microbubbles as novel molecular tracer.
S. Hernot (2012)
A direct comparison of contrast-enhanced ultrasound and dynamic contrast-enhanced magnetic resonance imaging for prostate cancer detection and prediction of aggressiveness
A. Baur (2017)
Ultrasound of prostate cancer: recent advances
L. Pallwein (2007)
Current status of transrectal ultrasound techniques in prostate cancer
M. Smeenge (2012)
Clearance Pathways and Tumor Targeting of Imaging Nanoparticles.
M. Yu (2015)
Cancer nanomedicine: progress, challenges and opportunities
J. Shi (2017)
Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases.
S. Sweat (1998)
EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent.
N. Mottet (2017)
First-in-Human Ultrasound Molecular Imaging With a VEGFR2-Specific Ultrasound Molecular Contrast Agent (BR55) in Prostate Cancer: A Safety and Feasibility Pilot Study
M. Smeenge (2017)
Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer
A. Ghosh (2004)
VEGFR 2 - specific ultrasound molecular contrast agent ( BR 55 ) in prostate cancer : a safety and feasibility pilot study
M. G. Schouten
Sink or float? Characterization of shell-stabilized bulk nanobubbles using a resonant mass measurement technique† †Electronic supplementary information (ESI) available: Experimental details, supporting information. See DOI: 10.1039/c8nr08763f
C. Hernandez (2019)
Direct Comparison of Targeted MRI-Guided Biopsy with Systematic Transrectal Ultrasound-Guided Biopsy in Patients with Previous Negative Prostate Biopsies
S. Kaufmann (2014)
Construction and In Vitro/In Vivo Targeting of PSMA‐Targeted Nanoscale Microbubbles in Prostate Cancer
Luo-fu Wang (2013)
Odyssey of a cancer nanoparticle: from injection site to site of action.
Joseph W. Nichols (2012)
Development of Targeted Near-Infrared Imaging Agents for Prostate Cancer
X. Wang (2014)
Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect.
H. Maeda (2009)
First-in-Man Evaluation of 2 High-Affinity PSMA-Avid Small Molecules for Imaging Prostate Cancer
John A. Barrett (2013)
Improving Conventional Enhanced Permeability and Retention (EPR) Effects; What Is the Appropriate Target?
Hisataka Kobayashi (2013)
Prospective randomized trial comparing magnetic resonance imaging (MRI)-guided in-bore biopsy to MRI-ultrasound fusion and transrectal ultrasound-guided prostate biopsy in patients with prior negative biopsies.
C. Arsov (2015)
This paper is referenced by
Contrast enhanced ultrasound imaging by nature-inspired ultrastable echogenic nanobubbles.
A. D. de Leon (2019)
Molecular Ultrasound Imaging
Gurbet Köse (2020)
Photoacoustic imaging biomarkers for monitoring biophysical changes during nanobubble-mediated radiation treatment
E. Hysi (2020)
Quantification of PSMA expression in prostate cancer by pharmacokinetic modeling of targeted ultrasound nanobubbles
S. Turco (2019)
Ultrasound Molecular Imaging of Cancer: Design and Formulation Strategies of Targeted Contrast Agents.
A. Klibanov (2020)
High yield, shell-stabilized, narrow-sized C3F8 nanobubbles with different shell properties and precisely controllable response to acoustic excitations: experimental observations and numerical simulations
A. J. Sojahrood (2020)
Contrast-enhanced ultrasound with sub-micron sized contrast agents detects insulitis in mouse models of type1 diabetes
D. Ramirez (2020)